Objective: To explore the longitudinal relationship between bullying victimization and sleep quality among rural boarding junior high school students in Hebei Province, and to investigate the chain mediated role of loneliness and rumination, so as to provide evidence for promoting sleep health in the population. Methods: A baseline survey was conducted in May, 2023 (T1) by convenient sampling method, and two rounds of longitudinal surveys were conducted in November, 2023 (T2) and May, 2024 (T3) among students in two rural boarding junior high schools in Hebei Province, and a sample of 601 students who completed all the surveys was finally obtained. Students completed questionnaires, including the Delaware Bullying Victimization Scale Student (DBVS-S), the University of California at Los Angeles Loneliness Scale (UCLA), the Ruminative Responses Scale, and the Pittsburgh Sleep Quality Index (PSQI). Group differences were examined by using t-test or ANOVA, correlations between variables were analyzed by using Pearson correlation coefficients, and a serial mediation structural equation model was constructed, with mediation effects tested via the Bootstrap method. Results: Female students scored higher on sleep quality than male students (7.47±2.70, 6.47 ±2.46, t =4.74, P <0.01). Pearson correlation analysis indicated that bullying victimization was positively correlated with loneliness, rumination, and sleep quality; loneliness was positively correlated with rumination and sleep quality; and rumination was positively correlated with sleep quality ( r =0.26, 0.33, 0.23; 0.39, 0.38; 0.54, all P <0.01). Mediation analysis showed that T2 loneliness had an independent mediating effect of 0.70 (95% CI =0.36-1.35) between T1 bullying victimization and T3 sleep quality, T2 rumination had an independent mediating effect of 1.34 (95% CI =0.71-2.45), and the serial mediation effect of T2 loneliness and T2 rumination was 0.64 (95% CI =0.37-1.13), accounting for 22.11% of the total effect (all P <0.01). Conclusions Bullying victimization adversely affects sleep quality among rural boarding junior high school students through a longitudinal chain mediating pathway involving loneliness and rumination. Psychological interventions should be strengthened for students who experience bullying to alleviate their loneliness and reduce rumination, thereby improving sleep quality.

This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

ObjectiveTo investigate the chemosensitization effect of gallic acid （GA） combined with sorafenib （Sora） on hepatocellular carcinoma HepG2 cells and related mechanisms. MethodsHepG2 cells were randomly divided into control group， GA group， Sora group， and GA+Sora group. CCK8 assay was used to measure cell viability； CompuSyn software was used to analyze combination index （CI）； colony formation assay was used to evaluate the colony formation ability of cells； flow cytometry was used to measure cell apoptosis； wound healing assay and Transwell chamber assay were used to observe the migration and invasion abilities of cells； Western Blot was used to measure the expression matrix metalloproteinase 2 （MMP-2）， matrix metalloproteinase 9 （MMP-9）， and apoptosis-related proteins. HepG2 cells were subcutaneously inoculated into the lower right back of mice， and 6 days later， the mice were divided into control group， GA group， Sora group， and GA+Sora group. Tumor size and body weight were measured once a week， and drug intervention was performed for 21 days. Then the nude mice were sacrificed， and tumor weight was measured. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe mean IC₅₀ values of GA and Sora for the treatment of HepG2 cells for 48 hours were 123.47±5.16 μmol/L and 9.87±0.98 μmol/L， respectively， and when Sora was combined with 70 μmol/L GA （IC₃₀）， IC₅₀ decreased to 2.06±0.35 μmol/L； the CI value was<1 for Sora at different concentrations combined with 70 μmol/L GA. The number of cell colonies was 234.0±20.4， 147.0±12.1， 129.3±13.3， and 73.0±7.6， respectively， in the four groups， and the GA+Sora group had a significantly lower number of cell colonies than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the cell apoptosis rate was 1.98%±0.29%， 15.17%± 1.56%， 18.65%±1.48%， and 34.60%±5.36%， respectively， in the four groups， and the GA+Sora group had a significantly higher cell apoptosis rate than the control group， the GA group， and the Sora group （all P<0.05）. After 24 hours of treatment， the cell migration rate was 55.59%±5.08%， 29.34%±4.36%， 21.80%±5.16%， and 6.47%±2.75%， respectively， in the four groups， and the GA+Sora group had a significantly lower cell migration rate than the control group， the GA group， and the Sora group （all P<0.05）. After 48 hours of treatment， the number of transmembrane cells was 223.7±13.0， 168.3±10.9， 155.3±29.1， and 62.7±19.7， respectively， in the four groups， and the GA+Sora group had a significantly lower number of transmembrane cells than the control group， the GA group， and the Sora group （all P<0.05）. Compared with the control group， the GA group， the Sora group， and the GA+Sora group had significant reductions in the protein expression levels of MMP-2， MMP-9， and Bcl-2 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. Compared with the control group， the GA， Sora， and GA+Sora groups had significant reductions in tumor volume and weight （all P<0.05）， and compared with the Sora group， the GA+Sora group had significant reductions in tumor volume and weight in nude mice （both P<0.05）. ConclusionGA can increase the sensitivity of HepG2 cells to Sora chemotherapy， possibly by promoting cell apoptosis and inhibiting cell migration and invasion after combination with Sora.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

ObjectiveTo investigate the effect of gallic acid （GA） on the proliferation， migration， invasion， and apoptosis of human hepatocellular carcinoma HepG2 cells and its mechanism. MethodsHepG2 cells were treated with different concentrations of GA （0， 5， 10， 20， 30， 40， and 50 μg/mL） for 24 and 48 hours， and CCK8 assay was used to measure cell viability and calculate IC₅₀. The experiment was divided into control group （HepG2 cells）， 5 μg/mL GA group， 10 μg/mL GA group， and 20 μg/mL GA group. Plate colony formation assay was used to evaluate the effect of GA on cell proliferation； wound healing assay and Transwell chamber assay were used to observe the effect of GA on cell migration and invasion； flow cytometry was used to observe the effect of GA on cell apoptosis； Western blot was used to measure the expression of matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-9 （MMP-9）， and apoptosis-related proteins. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe mean IC₅₀ value of GA on HepG2 cells was 38.02±2.58 μg/mL at 24 hours and 18.36±1.54 μg/mL at 48 hours. The number of cell colonies was 239.00±29.45 in the control group， 210.00±19.00 in the 5 μg/mL GA group， 144.33±16.03 in the 10 μg/mL GA group， and 57.00±9.55 in the 20 μg/mL GA group， suggesting that compared with the control group， each GA group had a significant reduction in cell colony formation ability （all P<0.05）. After 24 hours of treatment， the cell migration rate was 42.62%± 7.82% in the control group， 35.34%±6.42% in the 5 μg/mL GA group， 21.85%±4.42% in the 10 μg/mL GA group， and 12.57%± 3.54% in the 20 μg/mL GA group， respectively， in these four groups， and the number of transmembrane cells in these four groups was 230.30±15.30， 182.12±12.60， 137.20±7.50， and 124.40±6.80， respectively， suggesting that compared with the control group， each GA group had significant reductions in migration rate and the number of transmembrane cells （all P<0.05）. After 48 hours of treatment， the cell apoptotic rate was 0.67%±0.08% in the control group， 13.27%±1.07% in the 5 μg/mL GA group， 20.94%± 2.45% in the 10 μg/mL GA group， and 40.74%±2.63% in the 20 μg/mL GA group， and compared with the control group， each GA group had a significant increase in cell apoptosis rate （all P<0.05）. Compared with the control group， each GA group had significant reductions in the protein expression levels of MMP-2 and MMP-9 （all P<0.05） and significant increases in the protein expression levels of Bax and cleaved caspase-3 （all P<0.05）. ConclusionGA can inhibit the proliferation， migration， and invasion of HepG2 cells and promote the apoptosis of HepG2 cells， possibly by regulating MMP-2， MMP-9， and the apoptosis-related proteins Bax/Bcl-2.

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged